title: A novel nanoparticle containing MOG peptide with BTLA induces T cell tolerance and prevents multiple sclerosis.
abstract: Accumulative evidence demonstrates that multiple sclerosis (MS) is caused by activation of myelin Ag-reactive CD4+ T cells. Therefore, the CD4+ T cells specific for myelin Ag may be the important therapeutical target of MS. The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) may have a regulatory role in maintaining peripheral tolerance, however, its role in MS is still unknown. In this study, a novel nanoparticle containing MOG peptide with BTLA was designed and transduced into dendritic cells (DCs), and MOG peptide-induced EAE mice were administrated with the genetically modified DCs in vivo. The results demonstrated that modified DCs significantly enhanced the proportion of Foxp3+ CD4+ regulatory T cells, increased IL-10 and TGF-β cytokine secretion, while decreased IL-2 and IFN-γ cytokine secretion. Furthermore, modified DCs supressed the CD4+ T cell response to MOG, cell infiltration into spinal cord, and the severity of EAE. In contrast, immune response to irrelevant exogenous Ag was not impaired by treatment with modified DCs. These findings suggested that DCs transduced with nanoparticle could induce specific CD4+ T-cells tolerance, which provided a promising therapeutic means to negatively manipulate immune response for autoimmune diseases without inhibition of the immune response to irrelevant Ag.
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Yuan
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Fenlan
authors.initials: F
authors.lastname: Fu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Liu
authors.forename: Chuangan
authors.initials: C
authors.lastname: Lin
authors.forename: Xianqun
authors.initials: X
authors.lastname: Wu
authors.forename: Hanchao
authors.initials: H
authors.lastname: Shen
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018014:Gene Transfer Techniques; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000517:prevention & control*; D009186:Myelin Sheath / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000627:therapeutic use*; D053758:Nanoparticles / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: C488868:BTLA protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; C571327:Mog protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: BTLA; MOG peptide; Multiple sclerosis; Nanoparticle; T cell tolerance